title: Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.
abstract: Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration.
authors.affiliation: Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Kristian Vinter
authors.initials: KV
authors.lastname: Juul
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Nørgaard
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D050034:Antidiuretic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D055598:Chemical Phenomena; D002648:Child; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D020790:Diabetes Insipidus, Neurogenic / Q000188:drug therapy* / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced / Q000517:prevention & control; D007564:Japan; D008297:Male; D055595:Mechanical Phenomena; D008875:Middle Aged; D013607:Tablets; D055815:Young Adult
chemical_list: D050034:Antidiuretic Agents; D013607:Tablets; D003894:Deamino Arginine Vasopressin